Towards a micro-structural model of cardiac tissue based on confocal microscopy
Computational modeling is a major approach to gain insights into electrical signaling in normal and diseased cardiac tissue. Various types of models have been developed in the past including e.g. cellular automata and reaction-diffusion systems. In general, current approaches are based on two assumptions. Firstly cardiac muscle cells (myocytes) are the exclusive cell type in the heart. Secondly their shape is approximated well by simple geometries. However, cardiac tissue is known to be a material composed of various cell types including - in addition to myocytes - fibroblasts, myofibroblasts, endothelial, vascular smooth muscle, and neural cells. Some of these cell types are known to be electrically coupled to myocytes via gap junction channels. Development of novel approaches that include various cell types and realistic geometries appears necessary. With this additional information it will be possible to gain insights into electrical signaling at the microscopic level. Electrical excitation propagation at a cellular level of resolution is not well studied yet.
The envisioned model will be multi-domain, i.e. include multiple intra- and extracellular domains. The model will provide three-dimensional data at high spatial resolution (200nm) on cardiac cells of various types and their electrical coupling via intercellular connections together with the extracellular spaces. Future applications of this model will include computational studies of electrical conduction in cardiac tissue.
The necessary data to generate this model was obtained by fluorescence confocal microscopy. Afterwards it was necessary to develop tools to process and anallyse the data.